Decreased levels of Ca2+-calmodulin-dependent protein kinase IV in the testis as a contributing factor to reduced fertility in male Crybb2 -/- mice

Abstract

βB2-crystallin (Crybb2), a member of the βγ-crystallin superfamily, in conjunction with α-crystallin, constitute the major proteins of the mammalian eye lens. Crybb2 is also expressed outside the lens, and certain related functions in these tissues have been reported. In the present study, in order to define the physiological role of Crybb2, we generated mice with a targeted deletion of the Crybb2 gene. Surprisingly, fertility was markedly reduced in male homozygous knockout mice compared to wild-type (WT) mice. Further experiments were performed to explore the underlying mechanism of subfertility in male Crybb2-/- mice. Our results showed that Crybb2 was mainly expressed in the spermatogonia from the testes of mice with the WT C57BL/C genetic background. The testes of 4-week-old Crybb2-/- mice were significantly hyperplastic, and no significant difference was found within 3 weeks postpartum. Additionally, there was a marked increase in the proliferation and apoptosis of germ cells, and the biological defects of these cells correlated with the decreased Bcl-2 levels, which correlated with the reduction of Ca2+-calmodulin-dependent protein kinase IV (CaMKIV) in the testis. These results suggest that the reduced fertility of Crybb2 -/- male mice may result from the disordered proliferation and apoptosis of germ cells in the testis, possibly due to reduced CaMKIV from the loss of Crybb2.